Cancers develop over a period of several years and are characterized by molecular changes in cancer cells or tissue prior to noticeable symptoms (1). If such changes in tumor tissues can be detected in a patient's serum or blood, they can be used as biomarkers that could have a significant impact on clinical outcomes.
Within the past decade, advances in proteomic technologies have stimulated a search for serum biomarkers by profiling serum proteomic patterns (2,3). However, when these discriminatory proteins are identified, they have often turned out to be well-known high abundant classical plasma proteins or acute-phase proteins (6). Although these high abundant plasma proteins are indicators of interesting biology and have been shown to associate with different types of cancer (7), they are not likely derived from tumor tissue as specific tumor markers. Instead, useful serum biomarkers for tumor detection are those proteins released in small amounts specifically from tumors, indicated a specific response of the system to cancer cells, or entered to blood due to structural changes in the microenvironment surrounding cancer cells (8).
Ideally, if proteins from specific tumors can be detected in patients' blood and the abundance of these proteins in blood is associated with tumor development, these proteins can be used as candidate targets to develop assays for the detection of cancer in the specific tissue using blood tests.
Since the discovery of prostate-specific antigen (PSA), PSA as serum biomarker has been developed as the best serum marker for the early detection of cancer. The screening of prostate cancer using the PSA test has resulted in early intervention with effective treatments and decreased morbidity (13,14). PSA has specific expression in prostate with leakage to patients' blood during cancer development. However, PSA measurement has limitations, since the test is not specific for prostate cancer. PSA can also be elevated due to benign prostate diseases such as benign prostatic hyperplasia and prostatitis. The 4-10 ng/mL PSA range has been termed the “diagnostic gray zone” due to such overlap in PSA concentrations. Several studies have shown that a significant incidence of cancer (24.5%) occurs in men with total serum PSA concentrations between 2.5-4.0 ng/ml range, similar to the 4-10 ng/mL range (15), although it has also been recognized that prostate cancer can occur over all PSA ranges (16, 17).
Therefore, the need exists for new biomarkers that will increase the accuracy of prostate cancer detection.